ENANTIOSELECTIVE DISPOSITION OF IBUPROFEN IN ELDERLY PERSONS WITH ANDWITHOUT RENAL IMPAIRMENT

By using stable isotope methodology, we studied the disposition of ibu profen after the first and last dose of a 4-week regimen of 800 mg of racemic ibuprofen every 8 hr in three groups of subjects: 1) young hea lthy volunteers (n = 8); 2) healthy elderly volunteers (n = 14); and 3 ) elderly patients with creatinine clearance between 30 and 70 ml/min (n = 13). Stereoselective gas chromatography-mass spectrometry was use d to quantify deuterated S- and nondeuterated R- and S-ibuprofen in se rum up to 24 hr after the first and last doses. Urinary excretion of t he stereoisomeric forms of carboxyibuprofen, hydroxyibuprofen and ibup rofen glucuronide were determined up to 24-hr postdose by stereoselect ive high-performance liquid chromatography. Stereoselective serum prot ein binding was determined by ultrafiltration. Both elderly groups had significantly decreased binding of S-ibuprofen compared to the young group. The S-ibuprofen pharmacokinetics were significantly different i n the elderly patients with renal impairment compared to the young vol unteers: the T-1/2 was increased, the unbound clearance was decreased and the unbound concentration at steady state was increased. Fraction inverted was similar for all groups, but unbound clearances of glucuro nidation and hydroxylation were reduced in the elderly patients with r enal impairment. These results suggest that the disposition of ibuprof en enantiomers is altered in elderly persons with renal impairment; th ese changes may increase the risk for nonsteroidal anti-inflammatory d rug-associated adverse effects in such patients.